Biomonitoring of aromatic amines and alkylating agents by measuring hemoglobin adducts

Summary Analysis of hemoglobin adducts in blood samples is suitable for the biological monitoring of genotoxic chemicals. The method is specific because the compound to which the individual was exposed is identified. The sensitivity of the method depends on the analytical procedure applied, but is hardly limiting since large amounts of the protein can be obtained. The method provides not only information about the internal exposure to the environmental chemical, but also about the individual's capacity to generate ultimate genotoxic metabolites from it. Since macromolecular damage in blood cells is correlated to that in potential target tissues, this information is relevant to risk assessment, insofar as macromolecular damage produced by a specific chemical can be correlated with the development of tumors.     

Heterocyclic amines: evaluation of their role in diet associated human cancer

1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.     

Stress-induced changes in behavior and function of the neurohormonal systems in monkeys differing in social rank

Research Institute of Experimental Pathology and Therapy, Sukhumi. (Presented by Academician of the Russian Academy of Medical Sciences B. A. Lapin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 11, pp. 457–459, November, 1992.     

Probing the regioselective C‐deuteriation of lithium enolates derived from 2‐methyl‐tetralone in the presence of substituted tertiary amines

Results are reported on the regioselective C‐deuteriation of 2‐methyl‐tetralone using a series of D‐sources and tertiary amines as potential mediators. The results presented further aid the understanding of kinetic deuteriation of both ‘base‐containing’ and ‘base‐free’ enolates. Copyright © 2006 John Wiley & Sons, Ltd.     

Development of acute autoimmune encephalomyelitis in mice: Factors regulating the effector phase of the disease

The development of acute experimental autoimmune encephalomyelitis (EAE) in mice is potentiated by the use of Bordetella pertussis vaccine as an adjuvant. Histamine sensitizing factor (HSF) extracted from B. pertussis is the active adjuvant agent and causes a mild increase in cerebrovascular permeability. During the development of EAE, there is an additional increase in vascular permeability of the brain and spinal cord. The adjuvant action of B. pertussis HSF does not appear to mimic a generalized beta-adrenergic blockade, since the course of EAE is not potentiated by adrenalectomy. The cerebrovascular permeability changes observed in EAE are probably mediated by vasoactive amines, since the expression of EAE can be blocked by vasoactive amine antagonists.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

气相色谱-串联质谱法测定血清中的16种多环芳烃

目的 建立血清中16种多环芳烃的气相色谱-串联质谱测定方法。方法 血清样经甲醇沉淀蛋白,加入正己烷与二氯甲烷混合溶剂萃取,萃取物氮吹至近干后,正己烷和二氯甲烷混合溶剂复溶,取1 μl上清液进样分析。16种待测多环芳烃经DB-5色谱柱(30 m×0.25 mm,0.25 μm)分离,多反应监测模式监测,内标法定量。结果 本法在1.0 μg/L～2.0×10² μg/L范围内线性良好,方法检出限为4.20×10^-2 μg/L～0.27 μg/L,加标回收率为79.7%～108.0%,精密度为2.57%～6.76%。结论 本方法具有灵敏、快速、回收率和重复性好等优点,满足人血清中多种多环芳烃测定的要求。     

Gastric mucosal protection with β-phenylethylamine (PEA) and other sympathomimetic amines against absolute ethanol in the rat

The purpose of this study was to investigate the potential of -phenylethylamine (PEA), an amphetamine-like compound present in the blood during high stress situations, to protect rat gastric mucosa against absolute ethanol. F-344 rats were pretreated with PEA in saline at several dose levels and at various times prior to oral administration of 1 ml absolute ethanol. PEA at dose levels of 50 and 100 mg/kg significantly reduced the severity of alcohol-induced lesions following oral, but not parenteral, treatment. The duration of protection with PEA was approximately 90 min, with maximum protection observed when PEA was administered 15–30 min before alcohol. Pretreatment with indomethacin did not prevent or reduce the protection induced by PEA. Other sympathomimetic amines such as isoproterenol and ephedrin were similarly cytoprotective against absolute ethanol while amphetamine, phenylephrine, and epinephrine proved ineffective. These results add further support to the role of the sympathetic nervous system in regulating gastric mucosal protection in the rat.     

Biomonitoring of polycyclic aromatic hydrocarbons in highly exposed coke plant workers by measurement of urinary phenanthrene and pyrene metabolites (phenols and dihydrodiols)

Summary A filter combination consisting of an impregnated glass fibre and a control filter was used for the collection of air samples in which gaseous and particulate polycyclic aromatic hydrocarbons (PAHs) were determined. To estimate the loss of lower boiling PAHs, d₁₀-phenanthrene was applied as internal standard. A simple, well-reproducible method for the determination of 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1,2-, 3,4- and 9,10 dihydroxydihydrophenanthrene, 1-hydroxypyrene and 1,2-dihydroxy-1,2-dihydropyrene is described. By means of personal air samplers the exposure to PAHs of four coke plant employees working at different locations was measured over 4 days. Simultaneously the 24-h urine was collected and stored frozen until analysed. The main excretion product of pyrene is a 1-hydroxypyrene conjugate, whereas phenanthrene is excreted predominantly as dihydrodiol conjugate. As expected, workers on the battery topside were exposed the most and accordingly excreted by far the highest amounts of PAHs. Up to 34.0 g phenanthrol conjugates (total of all isomeric phenols) and 195.5 g dihydrodiol conjugates (total of all isomeric dihydrodiols) were excreted in the 24-h urine (mean of 4 days). The metabolite profiles of five isomeric phenanthrene phenols and three isomeric dihydrodiols exhibited only small percentage variations within one individual whereas significant interindividual differences were observed. These findings may indicate a genetically determined enzyme pattern responsible for the metabolic conversion of PAHs.This paper is dedicated to Professor Dr. R. Preußmann on the occasion of his 65th birthday     

Biological monitoring of occupational exposure to toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.